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Authors employ a cynomolgus macaque model to explore the protective potential of mucosal vaccination with Mycobacterium tuberculosis ΔsigH.

Serotonin is implicated in mood-related disorders, yet direct evidence linking it to disease precipitation or treatment remains limited. Here, authors show that histone serotonylation contributes to stress- and antidepressant-mediated phenotypes, which may be of clinical relevance.

The role of viral Fc-gamma receptors in rhesus cytomegalovirus (RhCMV) infection is unclear. Here, the authors characterized RhCMV vFcγRs and report that their deletion did not affect virus replication, tropism or superinfection in rhesus macaques but increased susceptibility of the virus to antibody control.

Enteropeptins are peptide natural products produced by the gut microbe Enterococcus cecorum. Now, the structure, biosynthesis and function of enteropeptins have been determined. After ribosomal biosynthesis, enteropeptins are post-translationally modified in three reactions carried out by a radical S-adenosylmethionine enzyme, an Mn²⁺-dependent arginase, and an Fe–S-containing methyltransferase, respectively, to form the N-methylornithine-containing peptide natural products.

Oxidative stress is associated with cardiovascular and neurodegenerative diseases. Here the authors show studies of transgenic chemogenetic mouse lines that develop sensory ataxia and cardiac hypertrophy caused by neurovascular oxidative stress.

After infection with SARS-CoV-2 a diverse set of symptoms remain or develop longer term in a condition termed long-CoVID, yet an accurate and tractable model has remained elusive. Here the authors present a non-human primate model of long-CoVID and show persistent hyperglycemia following acute infection.

Bicyclostreptins are peptide natural products in which a macrocyclic β-ether and a heterocyclic sp³–sp³ linkage between a backbone amide nitrogen and an adjacent α-carbon are installed by two radical S-adenosylmethionine metalloenzymes.

Khader and colleagues show Mycobacterium tuberculosis (Mtb)-specific B cells are needed to recruit T_FH cells into follicular-like structures within lung granulomas to control the Mtb bacilli; however, specific antibodies and many conventional properties of B cells are dispensable.

COVID-19 can result in neurological manifestations and animal models could provide insights into the mechanisms. Here, the authors describe neuroinflammation, microhemorrhages and brain hypoxia in SARS-CoV-2 infected non-human primates, including in animals that don’t develop severe respiratory disease.

Cutaneous squamous cell of the skin is a common neoplasm that frequently arises from precancerous actinic keratoses. Here, the authors carry out genomic analysis on matched sets of human lesions and compare with those in ultraviolet treated mice and identify conserved drivers of tumour development.

Using HIV Env protein immunogen priming in rhesus monkeys followed by a long period without further immunization, we demonstrate germinal centre B cells lasting at least 6 months, showing promise in regard to difficult vaccine targets.

To gain insights into the early immune dynamics of transcriptional changes during SARS-CoV-2 infection, Singh et al. provide longitudinal scRNA-Seq of the broncho-alveolar compartment of SARS-CoV-2 infected rhesus macaques. They observe an accumulation of a distinct macrophage population that possesses an interferon-driven innate anti-viral gene signature early during infection that correlates with viral clearance.

Insufficient glucagon signalling results in hyperaminoacidemia, which drives adaptive proliferation of glucagon-producing α cells. Here the authors report that the amino acid sensitive calcium sensing receptor (CaSR) is necessary for α cell proliferation via Gq signalling during hyperaminoacidemia.

Analysis of the phase 3 CheckMate 816 trial shows that the depth of pathologic response as assessed by percent residual viable tumor is correlated with event-free survival following neoadjuvant immunotherapy plus chemotherapy, supporting pathologic response as a biomarker of survival.

Trials in rhesus macaques show that a subunit vaccine against SARS-CoV-2, comprising the spike protein receptor-binding domain displayed on a nanoparticle protein scaffold, produces a robust protective response against the virus.

Here, Fahlberg et al. describe the cellular immune response during acute, resolving or progressive COVID-19 in SARS-CoV-2 infected non-human primates. The study identifies associations of monocytes and macrophage subtypes in lungs with disease outcome, IL-6 and IL-10 ratio in plasma, and viral replication in bronchial brushes.

HIV vaccine development can be aided by knowledge of correlates of protection. Here the authors identify engagement and reprogramming of tolerogenic CD14⁺ myeloid cells mediating a spatiotemporal balance of pro- and anti-inflammatory responses, as correlates of efficacy in female macaques vaccinated with the DNA/ALVAC/gp120/Alum platform.

The usual light conditions used in laboratories fail to mimic natural conditions. Here, by slightly modifying red/far-red ratios and temperature dynamics, the authors are able to faithfully reproduce natural spring flowering times and variation of the FT gene.

Analysis of mitochondrial genomes (mtDNA) by using whole-genome sequencing data from 2,658 cancer samples across 38 cancer types identifies hypermutated mtDNA cases, frequent somatic nuclear transfer of mtDNA and high variability of mtDNA copy number in many cancers.

Efficient, large-scale genomic analysis is facilitated on the cloud by a computational tool with error-diagnosing and self-healing capabilities.

Analysis of whole-genome sequencing data across 2,658 tumors spanning 38 cancer types shows that chromothripsis is pervasive, with a frequency of more than 50% in several cancer types, contributing to oncogene amplification, gene inactivation and cancer genome evolution.

Protein antigens, such as HIV envelope protein, require adjuvants for high immunogenicity. Here the authors show that a combined adjuvant approach with slow antigen delivery and potent ISCOMs adjuvant primes robust germinal center activity and humoral immunity in non-human primates. pSer-modified antigen shifts immunodominance to allow subdominant epitope-targeting of rare B cells.

Trace metals have been an important ingredient for life throughout Earth’s history. Here, the authors show that a member of an elusive archaeal lineage (Caldarchaeales or Aigarchaeota) requires tungsten for growth, and provide evidence that tungsten-dependent metabolism played a role in the origin and evolution of this lineage.

Neonates and infants infected with HIV generally develop disease rapidly, with early antiretroviral therapy (ART) often failing to achieve a sustained state of ART-free virologic remission. Here, the authors study viral reservoirs in neonatal macaques with early initiation of ART and an integrase inhibitor.

Alter and colleagues show that IgM titers in the plasma and bronchoalveolar lavage fluid represent markers of reduced Mtb burden in rhesus macaques vaccinated intravenously with Bacille Calmette–Guérin.

Zika virus (ZIKV) infection in pregnant women has been associated with fetal developmental defects. Here, the authors show that a Brazilian ZIKV isolate causes fetal demise in non-human primates and that antibody treatment at time of peak viremia is insufficient to clear ZIKV replication from amniotic fluid.

A comparison of related genomes provides valuable information about how they evolve. Here, the complete sequence of the smallest known nuclear genome from the microsporidiaE. intestinalis is described and compared with its larger sister E. cuniculi, revealing what parts are indispensable in even the most reduced genomes.

Madeleine Duvic, David Wheeler and colleagues present an integrated genomic analysis of Sézary syndrome. They identify recurrent alterations in key T cell signaling and differentiation genes and observe overexpression of IL32 and IL2RG in nearly all cases.

BCG, the only vaccine currently used against tuberculosis, confers only limited protection. Here the authors show that mucosal immunization of macaques with an attenuated strain of Mycobacterium tuberculosisconfers a high level of protection from a lethal challenge with the bacterium.

The authors find that the expression of the DNA methyltransferase Dnmt3a in mice is regulated by chronic cocaine and chronic social defeat stress in the nucleus accumbens. Manipulations that block DNA methylation potentiate cocaine reward and cause an antidepressant-like effect.

This study reports that the induction of the transcription factor ΔFosB is critical for mice to show resilience to the effects of chronic social defeat stress and for antidepressant responses in susceptible mice. ΔFosB acts to promote resilience by the induction of the GluR2 AMPA glutamate subunit, which decreases the responsiveness of nucleus accumbens neurons to glutamate.

Cissé, Ma et al. utilize genomic data from Pneumocystis species infecting macaques, rabbit, dogs and rats to investigate the molecular basis of host specificity in Pneumocystis. Their analyses provide insight to the specific adaptations enabling the infection of humans by P. jirovecii.

The development of the ureteral access sheath (UAS) has enabled substantially greater use of ureteroscopy for minimally invasive management of diseases of the upper urinary tract. Here, the authors describe the advantages and risks associated with the routine use of UAS, and the potential for use of UAS by endourologists for a wider range of applications.